There has been much interest in the mechanism of progressive renal insufficiency accompanying experimental renal injury and the role of altered glomerular hemodynamics. Recent results using this model indicate a critical role for thromboxane (TX) in the regulation of glomerular filtration rate (GFR) and blood pressure. GFR is normally related to tubular C1- reabsorption at the macula densa segment through a tubuloglomerular feedback process (TG). Glomerular hyperfiltration occurring in remnant nephrons of surgically-ablated kidneys increases delivery of filtrate to the loop of Henle and, therefore, might activate TG and limit the hyperfiltration. This hypothesis derives from our studies in normal dog and rat kidneys which have implicated TX in the TG response. Since TG may prevent excessive Na+ loss, and remnant nephrons of damaged kidneys must increase fractional Na+ excretion to maintain homeostasis, TX may limit Na+ excretion and thereby contribute to hypertension and progressive loss of renal function. I propose to vary the prostaglandin (PG) and TX contents of kidneys in the rat by changing dietary lipids affecting PG formation and by administering drugs which inhibit TX synthesis. I will use micropuncture methods in normal rats and rats with surgical reduction in renal mass to study the specific effects of PGs and TX on tubular NaC1 reabsorption in the proximal, loop and distal nephrons and their roles in regulating afferent and efferent arteriolar tone, glomerular pressures, flows and ultrafiltration coefficient and nephron plasma flow rate during activation of whole kidney TG. Understanding changes in glomerular hemodynamics and Na+ excretion occurring in rats whose diet has been specifically altered to vary PG and TX synthesis is important since dietary lipid intake can be altered in humans and, therefore, results from these studies could be beneficial in improving renal function in patients with otherwise progressive forms of chronic renal failure.